Maternal rat serum concentrations of dimethadione do not explain intra-litter differences in the incidence of dimethadione-induced birth defects, including novel findings in foetal lung

Rodger, Ian W.; Lam, Isabel; Thompson, M W; Rutter, Allison; Ozolins̆, Terence R.S.

doi:10.1016/j.tox.2014.10.014

Cited by 4 publications

(3 citation statements)

References 32 publications

(68 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The incidence of DMO-induced VSD in this study was 42.05%, which is somewhat different from the previously reported 65%~74% [ 8 , 9 ]. The possible reason is that some fetuses with edema have poor cardiac development, which is not conducive to supersonic observation.…”

Section: Discussioncontrasting

confidence: 99%

“…Dimethadione (DMO), the N-demethylated metabolite of trimethadione, resembles the teratogen and active metabolite of trimethadione [ 7 ]. With low maternal and fetal toxicity, DMO induces VSD at a rate of 65–74% during the key window of heart development in rats (from 8.5 days to 11 days of pregnancy) [ 8 , 9 ], while the natural incidence of cardiovascular malformations in Sprague-Dawley (SD) rats ranges only from 0.02 to 0.72% [ 10 ]. Besides, the success rate of DMO for inducing fetal VSD is significantly higher than that of sodium arsenic, homocysteine and VLA-4 antagonist derivatives [ 11 – 14 ].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The dimethadione-exposed rat fetus: an animal model for the prenatal ultrasound characterization of ventricular septal defect

Yang,

Lyu,

et al. 2023

BMC Cardiovasc Disord

View full text Add to dashboard Cite

Background Ventricular septal defect (VSD) is the most prevalent congenital heart disease (CHD) and is easily misdiagnosed or missed. An appropriate VSD animal model could be used to analyze the ultrasound characteristics and their related pathological bases, and provides the opportunity to further explore the pathogenesis of VSD. Currently, little is known about whether ultrahigh-frequency ultrasound biomicroscopy (UBM) is suitable to diagnose VSD of fetal rats. There is no research on whether a dimethadione (DMO)-induced fetal VSD model is suitable for the observation and analysis of imaging characteristics and the associated pathological basis. Methods We used DMO to induce VSD. UBM was used to perform the prenatal ultrasound characterization. With the pathological results used as the gold standard, the ultrasound characteristics and their related pathological bases were analyzed. Results The incidence of VSD in the DMO group was 42.05% and 39.71% (diagnosed by UBM and pathology, respectively, P > 0.05). The prenatal ultrasound findings and pathological basis of various diseases, including isolated VSD, complex CHD containing VSD, and extracardiac lesions, were detected and discussed. It was discovered that some fetuses showed features of noncompacted ventricular myocardium, and for the first time, clusters of red blood cell traversing the cardiomyocytes. Conclusions The DMO-induced VSD model is a low-cost model with a high success rate and is suitable for the observation and analysis of VSD. UBM is suitable for evaluating VSD.

show abstract

Section: Discussioncontrasting

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The dimethadione-exposed rat fetus: an animal model for the prenatal ultrasound characterization of ventricular septal defect

Yang,

Lyu,

et al. 2023

BMC Cardiovasc Disord

View full text Add to dashboard Cite

show abstract

“…Given the significant increases noted in the VM cultures, all four drugs progressed through to in vivo examination. Doses selected for investigation were in line with those used in previous unrelated rodent studies and fell significantly below known LD50 values 23–26 . Although both dimethadione and trazodone produced some elevation in FGF20 protein levels, these failed to reach significance.…”

Section: Discussionmentioning

confidence: 89%

Targeted repositioning identifies drugs that increase fibroblast growth factor 20 production and protect against 6-hydroxydopamine-induced nigral cell loss in rats

Fletcher

Jamieson

Williams

et al. 2019

Sci Rep

View full text Add to dashboard Cite

Endogenous fibroblast growth factor 20 (FGF20) supports maintenance of dopaminergic neurones within the nigrostriatal pathway. Moreover, direct intracerebral infusion of FGF20 protects against nigrostriatal tract loss in the 6-hydroxydopamine lesion rat model of Parkinson’s disease. Increasing endogenous FGF20 production might provide a less-invasive, more translational way of providing such protection. Accordingly, we adopted a targeted repositioning approach to screen for candidate FDA-approved drugs with potential to enhance endogenous FGF20 production in brain. In silico interrogation of the Broad Institute’s Connectivity Map database (CMap), revealed 50 candidate drugs predicted to increase FGF20 transcription, 16 of which had profiles favourable for use in Parkinson’s disease. Of these, 11 drugs were found to significantly elevate FGF20 protein production in MCF-7 cells, between two- and four-fold. Four drugs were selected for examination in vivo . Following oral dosing in rats for 7 days, salbutamol and triflusal, but not dimethadione or trazodone, significantly elevated FGF20 levels in the nigrostriatal tract. Preliminary examination in the unilateral 6-hydroxydopamine-lesioned rat revealed a modest but significant protection against nigral cell loss with both drugs. Our data demonstrate the power of targeted repositioning as a method to identify existing drugs that may combat disease progression in Parkinson’s by boosting FGF20 levels.

show abstract

Dimethadione embryotoxicity in the rat is neither correlated with maternal systemic drug concentrations nor embryonic tissue levels

Ozolins̆

Weston

Perretta

et al. 2015

Toxicology and Applied Pharmacology

View full text Add to dashboard Cite

Maternal rat serum concentrations of dimethadione do not explain intra-litter differences in the incidence of dimethadione-induced birth defects, including novel findings in foetal lung

Cited by 4 publications

References 32 publications

The dimethadione-exposed rat fetus: an animal model for the prenatal ultrasound characterization of ventricular septal defect

The dimethadione-exposed rat fetus: an animal model for the prenatal ultrasound characterization of ventricular septal defect

Targeted repositioning identifies drugs that increase fibroblast growth factor 20 production and protect against 6-hydroxydopamine-induced nigral cell loss in rats

Dimethadione embryotoxicity in the rat is neither correlated with maternal systemic drug concentrations nor embryonic tissue levels

Contact Info

Product

Resources

About